Developmental Biology Unit, UCL Institute of Child Health, London UK.
Stem Cells Transl Med. 2012 May;1(5):384-95. doi: 10.5966/sctm.2012-0009. Epub 2012 May 3.
Stem cells derived from adipose tissue are a potentially important source for autologous cell therapy and disease modeling, given fat tissue accessibility and abundance. Critical to developing standard protocols for therapeutic use is a thorough understanding of their potential, and whether this is consistent among individuals, hence, could be generally inferred. Such information is still lacking, particularly in children. To address these issues, we have used different methods to establish stem cells from adipose tissue (adipose-derived stem cells [ADSCs], adipose explant dedifferentiated stem cells [AEDSCs]) from several pediatric patients and investigated their phenotype and differentiation potential using monolayer and micromass cultures. We have also addressed the overlooked issue of selective induction of cartilage differentiation. ADSCs/AEDSCs from different patients showed a remarkably similar behavior. Pluripotency markers were detected in these cells, consistent with ease of reprogramming to induced pluripotent stem cells. Significantly, most ADSCs expressed markers of tissue-specific commitment/differentiation, including skeletogenic and neural markers, while maintaining a proliferative, undifferentiated morphology. Exposure to chondrogenic, osteogenic, adipogenic, or neurogenic conditions resulted in morphological differentiation and tissue-specific marker upregulation. These findings suggest that the ADSC "lineage-mixed" phenotype underlies their significant plasticity, which is much higher than that of chondroblasts we studied in parallel. Finally, whereas selective ADSC osteogenic differentiation was observed, chondrogenic induction always resulted in both cartilage and bone formation when a commercial chondrogenic medium was used; however, chondrogenic induction with a transforming growth factor β1-containing medium selectively resulted in cartilage formation. This clearly indicates that careful simultaneous assessment of bone and cartilage differentiation is essential when bioengineering stem cell-derived cartilage for clinical intervention.
脂肪组织来源的干细胞是自体细胞治疗和疾病建模的一个潜在的重要来源，因为脂肪组织易于获取且丰富。开发治疗用标准方案的关键是彻底了解其潜能，以及这种潜能在个体之间是否一致，因此可以普遍推断。然而，此类信息仍然缺乏，尤其是在儿童中。为了解决这些问题，我们使用不同的方法从小儿患者的脂肪组织中建立了干细胞（脂肪来源的干细胞 [ADSCs]，脂肪组织外植体去分化的干细胞 [AEDSCs]），并使用单层和微团培养来研究它们的表型和分化潜能。我们还解决了软骨分化的选择性诱导这一被忽视的问题。来自不同患者的 ADSC/AEDSC 表现出非常相似的行为。这些细胞中检测到多能性标记物，与易于重编程为诱导多能干细胞一致。重要的是，大多数 ADSC 表达组织特异性定向/分化的标记物，包括成骨和神经标记物，同时保持增殖、未分化的形态。暴露于软骨形成、成骨、成脂或神经发生条件下会导致形态分化和组织特异性标记物的上调。这些发现表明，ADSC 的“谱系混合”表型是其显著可塑性的基础，其可塑性远高于我们同时研究的软骨细胞。最后，虽然观察到 ADSC 的成骨选择性分化，但当使用商业软骨形成培养基时，软骨诱导总是导致软骨和骨的形成；然而，使用含有转化生长因子 β1 的培养基进行软骨诱导选择性地导致软骨形成。这清楚地表明，在进行基于干细胞的软骨生物工程以用于临床干预时，对骨和软骨分化的同时进行仔细评估至关重要。
